MIAMI BEACH, Fl -- March 15, 2000 - Reboxetine has surfaced as being well
tolerated and effective for the treatment of depression both in geriatric and
younger adult patients.

The data also suggests that reboxetine -- a novel, selective noradrenergic
reuptake inhibitor -- may be more effective than the selective serotonin
reuptake inhibitors (SSRIs) in younger adults with severe depression. The drug
might be particularly useful in restoring motivation, activity and social
function early in the recovery phase.

It also seems to lack adverse effects on cognition, including the sedative
and antimuscarinic effects of amitriptyline and other antidepressants, according
to Soo Borson, MD, professor in the department of psychiatry and behavioral
sciences and director of geropsychiatry services at University of Washington
School of Medicine, in Seattle, WA. Dr. Borson presented these findings on
reboxetine March 14, 2000 at the 13th Annual Meeting of the American Association
for Geriatric Psychiatry (AAGP), in Miami Beach FL.

Reboxetine seems to work by increasing noradrenergic availability. "We
know that norepinephrine is involved in regulating energy, drive and motivation.
Affective memory and fear conditioning are clearly involved. And we know that
noradrenergic mechanisms are involved in the neurovegetative functions-sleep,
regulating the sleep-wake cycle, regulating food intake, endocrine function and
peripheral sympathetic function. It's possible that movement-the initiation
speed and stamina of individuals-is conditioned in part by noradrenergic
mechanisms," Dr. Borson explained.

Reboxetine, a drug that has a selective noradrenergic effect, is the most
selective drug available. It is a norepinephrine reuptake blocker, which
interacts with a transporter and may have useful effects on age-related defects
in norepinephrine function.

There have been a few studies on the efficacy and safety of reboxetine on
geriatric depression.The first was an open-label study in 1999, followed by a
double-blind comparison with imipramine and a long-term continuation study
conducted in individuals who had responded acutely to reboxetine for major
depression.

According to Dr. Borson, reboxetine is as effective an antidepressant in
terms of responders, clinical global improvement and remission as the old
standards, such as imipramine. In comparison with imipramine in a double-blind,
randomized, controlled trial, there were fewer dropouts with reboxetine than
with imipramine. Side effects with imipramine that were more prominent than with
reboxetine were hypotension and death. Insomnia was the only side effect that
was more prominent with reboxetine-although the rates of 6 percent versus 3
percent were low. Side effects of dry mouth, constipation, nausea, sweating,
headache and urinary hesitancy/retention (especially in men) were equivalent for
the two drugs.

A long-term, open-label follow-up study conducted with people who had
responded to initial treatment followed the short-term study. Patients, with a
mean age of 74 years were administered 4 mg to 8 mg a day of reboxetine. One
hundred-sixty patients entered the trial; 139 entered the long-term phase; and
104 completed a year of treatment. About 66 percent of those initially treated
completed a long-term trial over a period of a year. Participants represented a
so-called "average" geriatric population with MDD or dysthymia.
Two-thirds of the participants were women.

The trial was unique in that people with medical co-morbidities were included.
They were not included if they had highly unstable medical disorders, but they
had a variety of conditions which are common among the elderly.

Those patients who improved with reboxetine over six weeks maintained their
gains over the long-term of the study, with an 87.8 percent response rate. The
drug was well tolerated over the long-term, with common side effects similar to
the short-term study.

Material that has been explored in younger adults but not yet in the
geriatric population shows few adverse effects on cognition or motor function in
younger adults who take reboxetine. This has been studied through choice
reaction time, driving performance and critical flicker fusion, which includes
the measure of attention and focus. Some suggest that there may be more rapid
improvement in social function with regard to reboxetine than with other
antidepressants and that there might be greater efficacy with reboxetine than
with SSRIs in severe depression. Measurements with younger adults also have
shown accelerated social recovery with reboxetine as compared to fluoxetine or
placebo.

Dr. Borson concluded that reboxetine is effective for major depression and
dysthymia. It is generally better tolerated. And though it tends to be safer in
patients with heart disease, there is a caveat regarding the presence of
underlying heart disease in very old people. More studies need to be done to
determine the efficacy of lower doses in very old, frail patients, he said.
Response rates are comparable to imipramine and published SSRI trials in the
elderly. Side effects are mild to moderate and the need to discontinue treatment
with reboxetine is unusual. Early response with reboxetine predicts long-term
outcome.

"This is what we need to do in geriatric psychiatry to further
understand this drug," she said. "We need to look at high-risk
subgroups; we need to look at cognitive, motor function and social recovery;
examine severe melancholic depression in older people -- it has only been done
in the young; and do direct comparisons with an SSRI and a combined reuptake
blocker."